生物活性

• 描述Phosphodiesterases (PDEs) comprise 11 enzyme families that hydrolyze adenosine 3′,5′ cyclic monophosphate and/or guanosine 3′,5′ cyclic monophosphate. Luteolin is a flavonoid that has been shown to inhibit PDE1-5 with IC50 values of around 20μM. The K_i values of luteolin against PDE1-5 were 15.0  3.9, 6.4  1.9, 13.9  4.2, 11.1  3.7 and 9.5  1.7μM, respectively. The EC50 (PDE4_H) value of luteolin for displacing 2nM [³H]-rolipram binding on the high-affinity rolipram binding sites was 11.2 ± 1.5μM^[9]. In RAW 264.7 cells, luteolin inhibited LPS-induced TNF-alpha release with an IC50 value of less than 1μM. Preincubation of cells with luteolin also inhibited LPS-induced phosphorylation of Akt and IkappaB-alpha^[10]. Treatment with luteolin (10 – 30μmol/kg, s.c.) significantly and dose-dependently shortened the duration of xylazine/ketamine-induced anesthesia. Also, luteolin inhibited 5nM [3^H]-flunitrazepam binding to rat cerebral cortex membranes with a K_i value of 60.1μM^[9].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  CHO cells	-	Function assay	-	Agonist activity at rat DAT expressed in CHO cells, EC50=1.45 μM	20971650
  HEK293 cells	-	Function assay	24 h	Agonist activity at mouse PPARgamma expressed in HEK293 cells co-expressing with Gal4 reporter vector after 24 hrs by dual-luciferase reporter assay, EC50=2.3 μM	24955889
  HEK293 FS cells	-	Function assay	-	Inhibition of NOX4 expressed in HEK293 FS cells assessed as H2O2 production by H2O2/Tyr/LPO assay, IC50=0.85 μM	20731357

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• 动物研究
  剂量	Mice: 0.2 mg/kg - 1 mg/kg[3] (i.p.), 5 mg/kg - 20 mg/kg[4] (i.p.); 0.1 mg/kg - 0.3 mg/kg[5] (i.g.); 0.1 mg/kg - 10 mg/kg[6] (p.o.) Rat: 50 mg/kg[7] (i.v.); 5 mg/kg - 20 mg/kg[8] (i.p.)
  给药途径	i.p., i.g., p.o., i.v.
  动物药代数据	Animal Rats[7] Dose 50 mg/kg Administration p.o. or i.v. F 4.10% (p.o.) Vdarea 27.58 L (i.v.) CL 2.14 L/h/kg (i.v.) AUC0→last 0.87 h·μg/ml (p.o.) 20.55 h·μg/ml (i.v.) AUC0→∞ 0.96 h·μg/ml (p.o.) 23.39 h·μg/ml (i.v.)

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02909686	Gulf War Illness	Not Applicable	Active, not recruiting	September 2019	United States, Alabama ... more >> University of Alabama at Birmingham Birmingham, Alabama, United States, 35294 Collapse <<
  NCT03365648	Allergic Rhinoconjunctivitis	Not Applicable	Completed	-	Italy ... more >> Fondazione IRCCS Policlinico San Matteo Pavia, (pv), Italy, 27100 Ospedale regionale San Salvatore - ASL 1 Avezzano Sulmona L'Aquila L'Aquila, AQ, Italy, 67100 A.O.U. Consorziale "Policlinico Giovanni XXIII" Bari, BA, Italy, 70126 A.O.U. Consorziale "Policlinico-Giovanni XXIII" Bari, BA, Italy, 70126 A.O.U. Policlinico Vittorio Emanuele Catania, CT, Italy, 95123 Istituto Giannina Gaslini Genova, GE, Italy, 16132 P.O. San Giovanni di Dio - ASP di Crotone Crotone, KR, Italy, 88900 A.O.U. Policlinico "G. Martino" Messina, ME, Italy, 98124 P.O. G. Salvini di Garbagnate Milanese - ASST Rhodense Garbagnate Milanese, MI, Italy, 20042 Ospedale Civile di Legnano - ASST Ovest Milanese Legnano, MI, Italy, 20162 Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, MI, Italy, 20122 Ospedale San Carlo Borromeo - ASST Azienda Socio Sanitaria Territoriale Santi Paolo E Carlo Milano, MI, Italy, 20157 Ospedale Città di Sesto San Giovanni - ASST Nord Milano Sesto San Giovanni, MI, Italy, 20099 Ospedale di Polistena "Santa Maria degli Ungheresi" - ASP di Reggio Calabria Polistena, RC, Italy, 89024 A.O.U. Policlinico Umberto I Roma, RM, Italy, 00161 P.O. di Busto Arsizio - ASST Valle Olona Busto Arsizio, VA, Italy, 21051 Az. Osp. Univ. dell'Università degli Studi della Campania "Luigi Vanvitelli" Napoli, Italy, 80138 Collapse <<
  NCT01971723	-	-	Completed	-	-

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• 参考文献

• [1] Yu MC, Chen JH, et al. Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [3H] -rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia. Eur J Pharmacol. 2010 Feb 10;627(1-3):269-75.

  [2] Xagorari A, Papapetropoulos A, et al. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2001 Jan;296(1):181-7.

  [3] Kotanidou A, Xagorari A, et al. Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of proinflammatory molecules in mice. Am J Respir Crit Care Med. 2002 Mar 15;165(6):818-23.

  [4] Tambe R, Patil A, et al. Assessment of luteolin isolated from Eclipta alba leaves in animal models of epilepsy. Pharm Biol. 2017 Dec;55(1):264-268.

  [5] Seelinger G, Merfort I, et al. Anti-carcinogenic effects of the flavonoid luteolin. Molecules. 2008 Oct 22;13(10):2628-51.

  [6] Das M, Ram A, et al. Luteolin alleviates bronchoconstriction and airway hyperreactivity in ovalbumin sensitized mice. Inflamm Res. 2003 Mar;52(3):101-6.

  [7] Pharmacokinetics of Luteolin and Metabolites in Rats

  [8] Wei B, Lin Q, et al. Luteolin ameliorates rat myocardial ischaemia-reperfusion injury through activation of peroxiredoxin II. Br J Pharmacol. 2018 Aug;175(16):3315-3332.

  [9] Yu MC, Chen JH, Lai CY, Han CY, Ko WC. Luteolin, a non-selective competitive inhibitor of phosphodiesterases 1-5, displaced [3H]-rolipram from high-affinity rolipram binding sites and reversed xylazine/ketamine-induced anesthesia. Eur J Pharmacol. 2010 Feb 10;627(1-3):269-75.

  [10] Xagorari A, Papapetropoulos A, Mauromatis A, Economou M, Fotsis T, Roussos C. Luteolin inhibits an endotoxin-stimulated phosphorylation cascade and proinflammatory cytokine production in macrophages. J Pharmacol Exp Ther. 2001 Jan;296(1):181-7.

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